Download Suggestion from clinicians

Chlorpromazine vs. Other Antipsychotics
Replacement/Addition to the List
Peer Feedback:
Multiple feedback obtained about replacement of chlorpromazine, also addition of quetiapine.
“replace with clozapine – Clozapine, although it has many adverse effects, is the most effective
for treating schizophrenia.”
“Chlorpromazine tends to be one of the worst tolerate antipsychotics
Quetiapine is an effective antipsychotic and has reasonable evidence as adjunct therapy in
depression and bipolar disorder”
“Current use (of quetiapine) exceeds evidence, but not including this would involve major shifts in
prescribing and may be difficult”
“Better options already on the list, e.g. Haldol”
“Clozapine. Unique. Only medication for treatment resistant schizophrenia. Not sure CPZ is
essential since have other 1st and 2nd generation antipsychotic options (haloperidol,
risperidone). Could consider a first generation depot formuation option.”
Note: Chlorpromazine and Haloperidol are 1st generation anti-psychotics; quetiapine, risperidone
and clozapine are 2nd generation antipsychotics. Chlorpromazine, Haloperidol, and Risperidone
are on the list.
Literature Review Questions:
What is the most efficacious treatment for schizophrenia?
Is Quetiapine more efficacious than Chlorpromazine?
Is Clozapine more efficacious than Chlorpromazine?
Is Haldol more efficacious than Chlorpromazine?
What is Quetiapine’s role in treating bipolar disorder and depression?
Literature Search:
Cochrane Review “antipsychotics AND efficacy AND (Chlorpromazine OR Haloperidol OR
Quetiapine OR Clozapine)”
Pubmed “chlorpromazine AND ((haloperidol OR haldol) OR quetiapine OR clozapine) AND
efficacy AND meta-analysis/review”,
CPG via the CMA ‘psychoses’
eCPS - Psychiatric Disorders: Psychoses
Haloperidol versus first-generation antipsychotics (Cochrane 2015)
The systematic review currently includes 63 randomised trials with 3675 participants. Bromperidol
(n = 9), loxapine (n = 7), and trifluoperazine (n = 6) were the most frequently administered
antipsychotics comparator to haloperidol. The included studies were published between 1962 and
1993, were characterised by small sample sizes (mean: 58 participants, range from 18 to 206)
and the predefined outcomes were often incompletely reported. All results for the main outcomes
were based on very low or low quality data. In many trials the mechanism of randomisation,
allocation, and blinding was frequently not reported. In short-term studies (up to 12 weeks), there
was no clear evidence of a difference between haloperidol and the pooled group of the other firstgeneration antipsychotic agents in terms of the primary outcome “clinically important response to
treatment” (40 RCTs, n = 2132, RR 0.93 CI 0.87 to 1.00). In the medium-term trials, haloperidol
may be less effective than the other first-generation antipsychotic group but this evidence is
based on only one trial (1 RCT, n = 80, RR 0.51 CI 0.37 to 0.69). Based on limited evidence,
haloperidol alleviated more positive symptoms of schizophrenia than the other antipsychotic
drugs. There were no statistically significant between-group differences in global state, other
mental state outcomes, behaviour, leaving the study early due to any reason, due to inefficacy, as
well as due to adverse effects. The only statistically significant difference in specific side effects
was that haloperidol produced less akathisia in the medium term.
The findings of the meta-analytic calculations support the statements of previous narrative,
unsystematic reviews suggesting comparable efficacy of first-generation antipsychotics. In
efficacy-related outcomes, there was no clear evidence of a difference between the prototypal
drug haloperidol and other, mainly high-potency first-generation antipsychotics. Additionally, we
demonstrated that haloperidol is characterised by a similar risk profile compared to the other firstgeneration antipsychotic compounds. The only statistically significant difference in specific side
effects was that haloperidol produced less akathisia in the medium term. The results were limited
by the low methodological quality in many of the included original studies. Data for the main
results were low or very low quality. Therefore, future clinical trials with high methodological
quality are required.
Dold, Markus, et al. "Haloperidol versus first-generation antipsychotics for the treatment of schizophrenia and other
psychotic disorders." status and date: New, published in 1 (2015).
Chlorpromazine versus every other antipsychotic for schizophrenia (2014)
Samara, Myrto T., et al. "Chlorpromazine versus every other antipsychotic for schizophrenia: A systematic
review and meta-analysis challenging the dogma of equal efficacy of antipsychotic drugs." European
Neuropsychopharmacology 24.7 (2014): 1046-1055.
2014 Delirium Guideline (Canadian Coalition for Seniors’ Mental Health)
Canadian Coalition for Seniors’ Mental Health; 2014 Guideline Update: The Assessment and
Treatment of Delirium
15 antipsychotic drugs in schizophrenia - meta-analysis (2013)
We emphasise that the differences in efficacy between drugs were small (standardised mean
differences 0·11–0·55, median 0·24), and smaller overall than those for side-effects. However, for
perspective, the efficacy differences compared with placebo were of only medium size (0·33–
0·88, median 0·44), so the differences in efficacy between drugs are possibly substantial enough
to be clinically important. Finally, because most clozapine studies were done in refractory
patients, clozapine is thought to be superior only in this subtype, but in our analysis of nonrefractory patients it was also more effective than all the other drugs. However, this result has the
limitation that it was mainly based on older comparisons of clozapine with first-generation drugs.
All-cause discontinuation has previously been used as a measure for the acceptability of
treatments, because it encompasses efficacy and tolerability.7,8 In our analysis, the results
paralleled the efficacy findings in that the most effective drugs also had the lowest discontinuation
rates (although haloperidol, the worst drug with respect to all-cause discontinuation, had a middle
rank for efficacy).
Haloperidol caused the most extrapyramidal side effects, followed by zotepine and
chlorpromazine. Chlorpromazine did not produce significantly more extrapyramidal side-effects
than did most second generation antipsychotics. Haloperidol doses lower than 7·5 mg per day
(the lowest dose in multiple-episode patients was 4 mg per day) produced similar outcomes for
efficacy and extrapyramidal side-effects as did higher doses. Clozapine has a low intrinsic risk of
extra pyramidal side-effects and might suppress both of these effects.
Weight gain and associated metabolic problems are regarded as the major issues associated
with new antipsychotic drugs. Indeed, olanzapine, zotepine, and clozapine were the worst in this
respect, and some guidelines recommend against the first-line use of olanzapine for first-episode
patients.12 However, ziprasidone and lurasidone (along with haloperidol) were the only
antipsychotic drugs without significantly more weight gain than placebo in adults. By contrast,
chlorpromazine was among the worst drugs in this respect.
Overall, our results with respect to sedation were reasonable, and direct and indirect comparisons
were consistent. For example, clozapine and chlorpromazine are certainly sedating drugs; the
good results for amisulpride can be accounted for by the absence of blockade of histaminergic
receptors associated with sedation; and the small sedative effects of paliperidone can possibly be
accounted for by its slow release mechanism limiting plasma peaks after ingestion.
QTc prolongation can lead to life-threatening torsades de pointes.50 The antipsychotic drugs
assessed differed enormously with respect to this outcome, with some not differing from placebo,
and one (sertindole) being almost one standard deviation worse. Indeed, sertindole was
associated with increased cardiac mortality compared with risperidone in a large, pragmatic,
randomised controlled trial51 (n=9858, all-cause mortality not different). In another study, 52 no
difference in frequency of sudden death was seen between ziprasidone (the third worst drug in
our analysis) and olanzapine (n=18 154).51 We emphasise that amisulpride was regarded as
benign in some guidelines,13 but our findings show that it might not be—a result that is consistent
with an analysis of amisulpride overdoses.50
Paliperidone and risperidone increased prolactin by more than one standard deviation compared
with placebo; aripiprazole reduced prolactin (although not significantly) because of its partialdopamine-agonist properties. Despite the collaboration of its manufacturer, no useable data on
amisulpride were available, but its high prolactin risk is well known.54
Leucht, Stefan, et al. "Comparative efficacy and tolerability of 15 antipsychotic drugs in
schizophrenia: a multiple-treatments meta-analysis." The Lancet382.9896 (2013): 951-962.
Cochrane Quetiapine vs Atypical Antipsychotics (2013)
Efficacy data tended to favour the control drugs over quetiapine (Positive and Negative Syndrome
Scale (PANSS) total score vs olanzapine: 11 RCTs, n = 1486, mean quetiapine endpoint score
3.67 higher, CI 1.95 to 5.39, low quality; vs risperidone: 13 RCTs, n = 2155, mean quetiapine
endpoint score 1.74 higher,CI 0.19 to 3.29, moderate quality; vs paliperidone: 1 RCT, n = 319,
mean quetiapine endpoint score 6.30 higher, CI 2.77 to 9.83, moderate quality), but the clinical
meaning of these data is unclear. No clear mental state differences were noted when quetiapine
was compared with clozapine, aripiprazole or ziprasidone. Compared with olanzapine, quetiapine
produced slightly fewer movement disorders (7 RCTs, n = 1127, RR use of antiparkinson
medication 0.51, CI 0.32 to 0.81, moderate quality) and less weight gain (8 RCTs, n = 1667, RR
0.68, CI 0.51 to 0.92, moderate quality) and glucose elevation, but increased QTc prolongation (3
RCTs, n = 643, MD 4.81, CI 0.34 to 9.28). Compared with risperidone, quetiapine induced slightly
fewer movement disorders (8 RCTs, n = 2163, RR use of antiparkinson medication 0.5, CI 0.36 to
0.69, moderate quality), less prolactin increase (7 RCTs, n = 1733, MD -35.25, CI -43.59 to 26.91) and some related adverse effects but greater cholesterol increase (6 RCTs, n =
1473,MD8.57, CI 4.85 to 12.29). On the basis of limited data, compared with paliperidone,
quetiapine induced fewer parkinsonian side effects (1 RCT, n = 319, RR use of antiparkinson
medication 0.64, CI 0.45 to 0.91, moderate quality) and less prolactin increase (1 RCT, n = 319,
MD -49.30, CI -57.80 to -40.80) and weight gain (1 RCT, n = 319, RR weight gain of 7% or more
of total body weight 2.52, CI 0.5 to 12.78, moderate quality). Compared with ziprasidone,
quetiapine induced slightly fewer extrapyramidal adverse effects (1 RCT, n = 522, RR use of
antiparkinson medication 0.43, CI 0.2 to 0.93, moderate quality) and less prolactin increase. On
the other hand, quetiapine was more sedating and led to greater weight gain (2 RCTs, n = 754,
RR 2.22, CI 1.35 to 3.63, moderate quality) and cholesterol increase when compared with
ziprasidone.
Available evidence from trials suggests that most people who start quetiapine stop taking it within
a few weeks (around 60%). Comparisons with amisulpride, sertindole and zotepine do not exist.
Although efficacy data favour olanzapine and risperidone compared with quetiapine, the clinical
meaning of these data remains unclear. Quetiapine may produce fewer parkinsonian effects than
paliperidone, aripiprazole, ziprasidone, risperidone and olanzapine. Quetiapine appears to have a
similar weight gain profile to risperidone, as well as clozapine and aripiprazole (although data are
very limited for the latter two comparators). Quetiapine may produce greater weight gain than
ziprasidone and less weight gain than olanzapine and paliperidone.Most data that have been
reported within existing comparisons are of very limited value because of assumptions and biases
within them.Much scope is available for further research into the effects of this widely used drug.
Clinicians should know that for only six of nine possible comparisons of quetiapine with other
second-generation antipsychotic drugs, relevant studies were identified, and that the evidence is
limited because very high numbers of participants leave the studies early. Our most robust finding
is that most people who are started on quetiapine will be off this drug within a few weeks.
Asmal, Laila, et al. "Quetiapine versus other atypical antipsychotics for schizophrenia." The Cochrane
Library (2013).
Cochrane Haldol vs Chlorpromazine (2008)
We found 14 relevant studies, mostly of short duration, poorly reported and conducted in the
1970s (total n=794 participants). Nine of these compared oral formulations of both compounds,
and five compared intramuscular formulations. Haloperidol was associated with significantly fewer
people leaving the studies early (13 RCTs, n=476, RR 0.26 CI 0.08 to 0.82). The efficacy
outcome ’no significant improvement’ tended to favour haloperidol, but this difference was not
statistically significant (9 RCTs, n=400, RR 0.81 CI 0.64 to 1.04). Movement disorders were more
frequent in the haloperidol groups (’at least one extrapyramidal side effect’: 6 RCTs, n=37, RR
2.2 CI 1.1 to 4.4, NNH5 CI 3 to 33), while chlorpromazine was associated with more frequent
hypotension (5 RCTs, n=175, RR 0.31 CI 0.11 to 0.88, NNH 7 CI 4 to 25). Similar trends were
found when studies comparing intramuscular formulations and studies comparing oral
formulations were analysed separately.
Given that haloperidol and chlorpromazine are global standard antipsychotic treatments for
schizophrenia, it is surprising that less than 800 people have been randomised to a comparison
and that incomplete reporting still makes it difficult for anyone to draw clear conclusions on the
comparative effects of these drugs. However, it seems that haloperidol causes more movement
disorders than chlorpromazine, while chlorpromazine is significantly more likely to lead to
hypotonia. We are surprised to have to say that we feel further, large, well designed, conducted
and reported studies are required.
Although haloperidol and chlorpromazine have been the standard drugs in the treatment of
schizophrenia for many years, there are relatively few studies investigating their efficacy and
tolerability head to head. There were no statistically significant efficacy differences between the
two compounds, but the side-effect profiles differ. Extrapyramidal side effects seem to be more
frequent when haloperidol is used, in comparison to which more hypotension is associated with
chlorpromazine treatment. Haloperidol and chlorpromazine are relatively cheap drugs, at least
compared to new, so called ’atypical’ antipsychotics. From the results of this review no definite
conclusions on the relative efficacy of the two compounds can be drawn, but their side-effect
profiles differ.
Leucht, Claudia, et al. "Haloperidol versus chlorpromazine for schizophrenia."Cochrane Database Syst Rev 1 (2008).
eCPS (2014)
Class
Drug
Antipsychotics chlorpromazi
, Firstne
generation,
generics
low potency
Antipsychotics haloperidol
, Firstgenerics
generation,
high potency
Dose
Adverse Effects
Comments
Advise
patients
about
antipsychotic
-associated
body
temperature
dysregulation
and
prevention of
heat stroke
(e.g.,
hydration,
sun
protection).
$$
Liver function
abnormalities.
Additive effects with other
CNS depressants,
anticholinergics, alphaadrenergic antagonists;
inhibitors of cytochrome
P450 enzymes (e.g., TCAs,
fluoxetine, fluvoxamine,
paroxetine) may increase
serum levels; inducers of
cytochrome P450 enzymes
(e.g., carbamazepine,
phenytoin) may decrease
serum levels; effects of
levodopa may be
inhibited.
More common with lowpotency agents:
sedation, cardiovascular
effects, anticholinergic
effects, weight gain,
lower seizure threshold,
Additive effects with other
CNS depressants,
anticholinergics, alphaadrenergic antagonists;
inhibitors of cytochrome
P450 enzymes (e.g., TCAs,
Advise
patients
about
antipsychotic
-associated
body
$
Initial:50–100
mg/day po
Usual:200–400
mg/day po
More common with lowpotency agents:
sedation, cardiovascular
effects, anticholinergic
effects, weight gain,
Maximum:1000 lower seizure threshold,
–2000
photosensitivity.
mg/daypo
More common with highpotency agents:
Divided in 1–3
increased prolactin, EPS,
doses/day
NMS, tardive movement
disorders.
Initial: 1.5–3
mg/day po
Usual: 4–12
mg/day po
Maximum: 20
Cos
ta
Drug Interactions
Class
Drug
Dose
mg/day po
Divided in 1–3
doses/day
Adverse Effects
Drug Interactions
Comments
photosensitivity.
More common with highpotency agents:
increased prolactin, EPS,
NMS, tardive movement
disorders.
fluoxetine, fluvoxamine,
paroxetine) may increase
serum levels; inducers of
cytochrome P450 enzymes
(e.g., carbamazepine,
phenytoin) may decrease
serum levels; effects of
levodopa may be
inhibited.
temperature
dysregulation
and
prevention of
heat stroke
(e.g.,
hydration,
sun
protection).
Liver function
abnormalities.
Legend:
Class
Antipsychotic
s, Secondgeneration
$ < $25
Drug
clozapine
Clozaril,
generics
$$ $25–50
$$$ $50–75
Cos
ta
Adverse Effects
Drug Interactions
Comments
Initial:12.5–25
mg/day po
Titration:
Increase
by 12.5–25
mg on 2nd day
and then by 25–
50 mg daily po
depending on
tolerance
Agranulocytosis
(<1%), seizures
(1–5%; doserelated), sedation,
orthostatic
hypotension,
tachycardia, fever,
nausea, weight
gain,
hypersalivation
(30–50%), urinary
incontinence;
increased risk of
diabetes and
hyperlipidemia;
myocarditis and
other cardiac
effects
(seePharmacologic
Choices).
Additive sedation with CNS
depressants; may potentiate
antihypertensive drug effects;
inhibitors of CYP1A2, such as
diltiazem, fluvoxamine or
propranolol, or of CYP3A4,
such as clarithromycin,
erythromycin, grapefruit juice
or prednisone, may increase
clozapine levels; inducers of
CYP1A2 or CYP3A4 such as
carbamazepine, phenytoin,
rifampin or cigarette smoking
may reduce clozapine levels;
respiratory depression with
higher doses of
benzodiazepines; avoid use
with bone marrow
suppressants and drugs that
lower the seizure threshold.
Advise
patients
about
antipsychoti
c-associated
body
temperature
dysregulatio
n and
prevention
of heat
stroke (e.g.,
hydration,
sun
protection).
$$
Sedation, dizziness,
weight gain,
orthostatic
hypotension,
hepatic
aminotransferase
elevation,
headache,
anticholinergic
effects, increased
risk of diabetes and
dyslipidemia,
possible increased
risk of cataracts;
may reduce thyroid
hormone levels.
Additive sedation with CNS
depressants; may potentiate
antihypertensive drug effects;
inhibitors of CYP3A4 (e.g.,
clarithromycin, erythromycin,
grapefruit juice, ketoconazole,
prednisone) may increase
quetiapine levels; inducers of
CYP3A4 (e.g., carbamazepine,
phenytoin, rifampin) may
decrease quetiapine levels.
Advise
patients
about
antipsychoti
c-associated
body
temperature
dysregulatio
n and
prevention
of heat
stroke (e.g.,
hydration,
sun
protection).
$
Advise
patients
$
Maximum: 900
mg/day
Divided in 1–3
doses/day
quetiapine
immediaterelease
Seroquel,
generics
$$$$ $75–100
Dose
Usual:300–600
mg/day po
Antipsychotic
s, Secondgeneration
Cos
ta
Initial: 50–100
mg/day po
Titration:
Increase by 100
mg/day
Usual: 600
mg/day
Maximum:800
mg/day(product
monograph).
Doses of up to
1200 mg/day
used in clinical
practice under
care of a
psychiatrist
Divided in 1–3
doses/day
Antipsychotic
s, Second-
quetiapine
extended-release
Initial: 300 mg
Sedation, dizziness, Additive sedation with CNS
QHS po (200 mg weight gain,
depressants; may potentiate
Class
Drug
Dose
Adverse Effects
antihypertensive drug effects;
inhibitors of CYP3A4 (e.g.,
clarithromycin, erythromycin,
grapefruit juice, ketoconazole,
prednisone) may increase
quetiapine levels; inducers of
CYP3A4 (e.g., carbamazepine,
phenytoin, rifampin) may
decrease quetiapine levels.
about
antipsychoti
c-associated
body
temperature
dysregulatio
n and
prevention
of heat
stroke (e.g.,
hydration,
sun
protection).
Cos
ta
Seroquel XR,
generics
Antipsychotics,
Secondgeneration
risperidone
Initial:0.5–1
mg/day po
Titration: Increase
Risperdal
Preparations, generi by 0.5–1 mg
poevery 3–4 days
cs
Usual:2–6 mg/day
po
Maximum: 6
mg/day po
Frequency: 1
dose/day,
preferably QHS
Sedation, headaches,
weight gain,
orthostatic
hypotension, rhinitis,
anxiety, dose-related
hyperprolactinemia
and EPS.
Additive sedation with CNS

depressants; may potentiate
antihypertensive drug effects;
inhibitors of CYP3A4 (e.g.,
clarithromycin, erythromycin,
grapefruit juice, ketoconazole,
prednisone) may increase
risperidone levels; inducers of
Risk of intraoperative
CYP3A4 (e.g., carbamazepine,
floppy iris syndrome in phenytoin, rifampin) may
patients undergoing
decrease risperidone levels.
cataract surgery who
have been exposed to
risperidone.
Advise
patients about
antipsychoticassociated
body
temperature
dysregulation
and
prevention of
heat stroke
(e.g.,
hydration, sun
protection).
$
Antipsychotics,
Secondgeneration
risperidone longacting injection
Sedation, headaches,
weight gain,
orthostatic
hypotension, rhinitis,
anxiety, dose-related
hyperprolactinemia
and EPS.
Additive sedation with CNS

depressants; may potentiate
antihypertensive drug effects;
inhibitors of CYP3A4 (e.g.,
clarithromycin, erythromycin,
grapefruit juice, ketoconazole,
prednisone) may increase
risperidone levels; inducers of
Risk of intraoperative
CYP3A4 (e.g., carbamazepine,
floppy iris syndrome in phenytoin, rifampin) may
patients undergoing
decrease risperidone levels.
cataract surgery who
have been exposed to
risperidone.
Advise
patients about
antipsychoticassociated
body
temperature
dysregulation
and
prevention of
heat stroke
(e.g.,
hydration, sun
protection).
$$$
Legend:
$ < $150
orthostatic
hypotension,
hepatic
aminotransferase
elevation,
headache,
anticholinergic
effects, increased
risk of diabetes and
Usual: 400–800 dyslipidemia,
mg/day
possible increased
risk of cataracts;
Given as a once- may reduce thyroid
daily dose,
hormone levels.
generally in the
evening
Comments
generation
Risperdal Consta
for first-episode
psychosis)
Titration: May
increase dose in
increments
of≤300
mg/day at
intervals ≥1 day
Drug Interactions
Initial: 25 mg im
every 2 wk (oral
supplementation
with current
antipsychotic
required for first 3
wk)
Titration:
Depending on
response, increase
by 12.5 mg every
4–8 wk
Usual: 25–37.5
mgim every 2 wk.
Some patients can
be maintained on
a dose of 12.5 mg
every 2 wk
Maximum: 50 mg
im every 2 wk
$$ $150–350
Adverse effects may
be less severe
compared to oral
risperidone due to
decreased peak to
trough serum
fluctuations.
$$$ $350–550
Sedation
Insomnia
Extrapyramidal
Side
Effectsa
clozapine
++++
–
–
++++
++++
–
++
quetiapine
+++
–
–
+++
++
–
+
risperidone
+
+
+++
++
+/–
+++
+
Drug
Weight
Metabolic
Gain
Abnormalitiesb Hyperprolactinemia
Cardiovascular
Effectsc
Legend: ++++ = high; +++ = moderate; ++ = low; + = very low; +/– = minimal or none; – = equivalent to
placebo
Psychiatric Disorders: Psychoses; Heather Milliken, MDCM, FRCPC, CSPQ; Date of revision:
September 2014
Quetiapine CPS for depression and bipolar disorder (2015)
Extended-release quetiapine, a second-generation or “atypical” antipsychotic agent, has been
approved in Canada for the treatment of depression and is considered to be a second-line
option.20 , 42
Psychiatric Disorders: Depression; Sidney H. Kennedy, MD, FRCPC, Sagar V. Parikh, MD,
FRCPC, and Sophie Grigoriadis, MD, PhD, FRCPC; Date of revision: March 2015
Quetiapine is listed as a first line therapy in Pharmacologic Management of Acute Mania, Acute
Depression, and Maintenance Treatment Regimens for Bipolar Disorder.
Psychiatric Disorders: Bipolar Disorder; Sagar V. Parikh, MD, FRCPC; Date of revision: April
2015
Medication
Uses
Chlorpromazine
delusions,
dementia,
hallucinations,
delirium in HIV,
porphyria,
schizophrenia
haloperidol
delusions,
hallucinations,
dementia
risperidone
bipolar disorders,
irritability
associated with
autistic disorder,
schizophrenia adults,
adolescents
Contraindications (CI),
drug interactions (DI) or
cautions
CI: comatose states or the
presence of large amounts of
CNS depressants (alcohol,
barbiturates, narcotics)
DI: phenytoin, propanalol,
thiazide diuretics,
anticoagulants Increased
risk for cardiovascular events
in elderly
CI: severe toxic CNS
depression or comatose
states, parkinson’s, dementiarelated psychosis
CI: epilepsy, thyrotoxicosis,
Parkinson’s disease, caution
with renal or hepatic
impairment, cardiovascular
disease, pregnancy
DI: fluoxetine, paroxetine,
quinidine, carbamazepine,
phenytoin, rifampin,
phenobarbital Elderly
patients at increased risk of
death
Adverse Effects
(common and
severe)
drowsiness, jaundice,
agranulocytosis,
hypotensive effects,
ECG changes, EPS,
tardive dyskinesia
delirium, confusion,
anticholinergic,
sedation, EPS,
akathisia,
neuropleptic
malignant syndrome,
tardive dyskinesia
increased appetite,
fatigue, nausea,
vomiting,
constipation,
parkinsonism, upper
abdominal pain,
anxiety, dizziness,
tremor, sedation,
akathisia, dystonia,
blurred vision,
stomach discomfort
Initial dose; typical
dose
Monitoring
10mg; 10mg every 8-6
hours OR 25mg every 8-6
hours trirate 1-2days, by
25-50mg semi-weekly,
max 2000mg/day)
Porphyria: 25-50mg
every 8-6 hours
0.25mg; 0.25-0.5mg
every 8-12 hours
BP, clinical
worsening
and suicidal
risk,
electrolytes
3mg; 3mg every 12 hours
clinical
worsening
and suicidal
risk, signs of
hypotension
(BP)